International Journal of Pharmaceutics最新文献_第9页

Hyaluronic/Poloxamers-co-decorated nanoemulsion containing naringenin and quercetin for psoriasis treatment 含柚皮素和槲皮素的透明质/poloxamers-共修饰纳米乳治疗银屑病。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-22 DOI: 10.1016/j.ijpharm.2026.126617

Ryan Fauzy , Fatimah Aqilah Az Zahro , Vania Maharani , Zaizafun Faiha , Angela Bilqisth , Syaiful Choiri

Psoriasis is a chronic autoimmune disorder characterized by persistent inflammation that progressively impairs the quality of life. Conventional corticosteroids suppress inflammatory mediators but fail to inhibit immune cell activation, leading to chronicity and long-term adverse effects. Quercetin and naringenin exhibit potent and synergistic antioxidant and anti-inflammatory properties, but their efficacy is hindered by low solubility and permeability. This study developed a quercetin–naringenin nanoemulsion hydrogel patch (NE–QNH) decorated with a hyaluronate–phospholipid complex (HA–PC) and modified with thermoresponsive polymers for targeted and controlled delivery. The nanoemulsion was optimized using a 2² factorial design based on critical quality attributes, including droplet size, polydispersity index, zeta potential, and encapsulation efficiency (EE). Hydrogel patches with varying polymer were evaluated for viscosity, drying time, spreadability, and elasticity. Ex-vivo permeation studies were conducted using porcine skin, and in-vivo efficacy was confirmed in a psoriasis model to validate the therapeutic outcome. The optimized NE–QNH exhibited a particle size of 14.94 ± 0.06 nm, a zeta potential of –9.78 ± 0.20 mV, an effective EE exceeding 80%, and high stability. The HA–PC complex decorated 87% of the nanoemulsion surface, while polymer modification formed an external matrix. Ex-vivo and in-vivo studies demonstrated a 240% increase in permeation and a 290% improvement in retention, epidermal recovery, and a significant reduction in psoriasis area and severity index, indicating that NE–QNH is a promising strategy for psoriasis therapy.

牛皮癣是一种慢性自身免疫性疾病，其特征是持续炎症，逐渐损害生活质量。传统的皮质类固醇抑制炎症介质，但不能抑制免疫细胞激活，导致慢性和长期的不良反应。槲皮素和柚皮素表现出强大的协同抗氧化和抗炎特性，但其低溶解度和渗透性阻碍了其作用。本研究开发了一种槲皮素-柚皮素纳米乳水凝胶贴片（NE-QNH），该贴片由透明质酸-磷脂复合物（HA-PC）修饰，并用热响应性聚合物（P188/P407）修饰，用于靶向和控制递送。基于液滴大小、多分散性指数、zeta电位和包封效率等关键质量属性，采用22因子设计对纳米乳进行优化。对不同HPMC的水凝胶贴片的粘度、干燥时间、涂抹性和弹性进行了评估。用猪皮进行了离体皮肤动力学研究，并在牛皮癣模型中证实了体内疗效，以验证治疗结果。优化后的NE-QNH粒径为14.94 ± 0.06 nm， zeta电位为-9.78 ± 0.20 mV，包封效率超过80%，稳定性好。HA-FP配合物修饰了87%的纳米乳液表面，而聚合物修饰形成了一个外部基质。体外和体内研究表明，NE-QNH的渗透性增加了240%，保留率和表皮恢复率提高了290%，PASI显著降低，这表明NE-QNH是一种很有前景的银屑病治疗策略。

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引用次数: 0

Terahertz imaging of titanium dioxide-free film coating hydration and tablet core interactions 无二氧化钛薄膜涂层水化与片剂芯相互作用的太赫兹成像。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-15 DOI: 10.1016/j.ijpharm.2026.126596

Mingrui Ma , Marwa Nassar , Jason Teckoe , J. Axel Zeitler

Titanium dioxide (TiO₂) is often used as a white base pigment in film coatings, but recent EU restrictions on its use in food have prompted pharmaceutical manufacturers to seek alternatives. Terahertz pulsed imaging (TPI) was used to examine the hydration of TiO₂-free immediate release formulations, either without an opacifier or using calcium carbonate (CaCO₃). The coatings, made from polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC), were approximately 100 µm thick. TPI results indicated that the type of film coating influenced hydration and scattering effects. However, there was no evidence that TiO₂-free coatings compromised tablet disintegration. Although the HPMC coating with CaCO₃ gelled upon hydration, the tablets fully hydrated within the required time. These findings offer insights into the mechanistic impacts of alternative coatings in the industry.

二氧化钛（TiO2）通常被用作薄膜涂料中的白色基础颜料，但最近欧盟对其在食品中的使用的限制促使制药商寻求替代品。使用太赫兹脉冲成像（TPI）来检查无tio2立即释放配方的水化作用，无论是不添加不透明剂还是使用碳酸钙（CaCO3）。涂层由聚乙烯醇（PVA）或羟丙基甲基纤维素（HPMC）制成，厚度约为100微米。TPI结果表明，薄膜涂层类型影响水化和散射效果。然而，没有证据表明无tio2涂层会影响片剂的崩解。虽然含有CaCO3的HPMC涂层在水化后会凝胶化，但片剂在规定的时间内完全水化。这些发现为工业中替代涂料的机械影响提供了见解。

引用次数: 0

Localized treatment of oral ulcers via responsive microneedle patch by enhancing mucosal penetration 反应性微针贴片增强粘膜穿透性局部治疗口腔溃疡。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-20 Epub Date: 2026-01-18 DOI: 10.1016/j.ijpharm.2026.126598

Junhua Xu , Haochen Wang , Kaizhi Li , Shulei Pan , Gang Guo , Kaiyun Liu , Ning Wang , Lin Xiang

Oral ulcers are a common and painful condition. Current treatments, including topical corticosteroids like dexamethasone, are hindered by poor drug penetration and systemic side effects. To address these challenges, we developed a dissolving microneedle patch incorporating protease-responsive gelatin nanoparticles encapsulating dexamethasone (DEX@GNPs) for localized delivery to the oral mucosa. This system is engineered to penetrate the mucosal barrier and release dexamethasone in response to the inflammatory microenvironment, thereby enhancing drug deposition at the ulcer site. In a rat buccal ulcer model, the DEX@GNP-loaded microneedles effectively delivered dexamethasone to the target tissue layers, significantly reduced ulcer size and promoted tissue regeneration. Moreover, the responsive release of dexamethasone in the presence of elevated protease levels was associated with a marked reduction in inflammation, as evidenced by decreased levels of key pro-inflammatory cytokines. These findings indicate that DEX@GNP-loaded microneedles provide a promising approach for the localized treatment of oral ulcers and may help to improve therapeutic outcomes by enabling efficient localized corticosteroid delivery.

口腔溃疡是一种常见且痛苦的疾病。目前的治疗方法，包括局部皮质类固醇如地塞米松，由于药物渗透性差和全身副作用而受到阻碍。为了解决这些挑战，我们开发了一种溶解性微针贴片，将蛋白酶反应性明胶纳米颗粒包裹地塞米松（DEX@GNPs），用于局部递送到口腔粘膜。该系统被设计为穿透粘膜屏障并释放地塞米松以响应炎症微环境，从而增强药物在溃疡部位的沉积。在大鼠口腔溃疡模型中，DEX@GNP-loaded微针有效地将地塞米松输送到目标组织层，显著减小溃疡大小，促进组织再生。此外，在蛋白酶水平升高的情况下，地塞米松的反应性释放与炎症的显著减少有关，关键的促炎细胞因子水平下降证明了这一点。这些发现表明DEX@GNP-loaded微针为口腔溃疡的局部治疗提供了一种有希望的方法，并可能通过有效的局部皮质类固醇递送来帮助改善治疗结果。

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引用次数: 0

Comparison and validation of a high-throughput lipid nanoparticle production and characterization workflow 高通量脂质纳米颗粒生产和表征工作流程的比较和验证。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-10 Epub Date: 2026-01-07 DOI: 10.1016/j.ijpharm.2026.126581

Simone Misto , Teresa Ferrillo , Sandor Balog , Fabiana Quaglia , Thomas Lee Moore

Lipid nanoparticle-borne, RNA-based therapeutics have emerged as transformative tools in nanomedicine. However, to optimize lipid nanoparticle (LNP) formulations against different pathologies, it will be necessary to change LNP payload, lipid composition, and production parameters. High-throughput formulation screening provides a way to rapidly develop and assess new LNP formulations, however this requires the capacity for high-throughput LNP physico-chemical characterization methods. When considering a shift towards automated/semi-automated high-throughput methods, it is pertinent to evaluate whether such characterization is comparable to so-called “tried and true” methods, especially in the context of scaling hit formulations from the screening phase to production. Here, we show that combining a semi-automated microfluidic system with a high-throughput characterization instrument enables the rapid production and characterization of LNP. Compared to conventional methods, the high-throughput plate reader DLS provided comparable hydrodynamic diameter data and faster analysis, albeit with lower sensitivity for RNA quantification. Additionally, we conducted an independent analysis of raw autocorrelation function data from dynamic light scattering measurements to mitigate functional differences between the high-throughput and single sample instruments. Fluorescence-based assays, also capable for high-throughput workflows, were demonstrated to be more sensitive for RNA quantification. These results illustrate that high-throughput systems can streamline LNP development, and be integrated into a translational workflow, i.e. screening to identify hit formulations, transition of hit formulations to scalable production methods, and validation of screening characterization results. This integrated workflow represents an important step for RNA therapeutic development pipelines, where increasing characterization capacity can accelerate nanomedicine development.

脂质纳米颗粒为载体，基于rna的治疗方法已经成为纳米医学的变革性工具。然而，为了优化脂质纳米颗粒（LNP）配方，有必要改变LNP的有效载荷、脂质组成和生产参数。高通量配方筛选为快速开发和评估新的LNP配方提供了一种方法，但这需要高通量LNP物理化学表征方法的能力。当考虑转向自动化/半自动化的高通量方法时，评估这种表征是否与所谓的“可靠的”方法相媲美是相关的，特别是在从筛选阶段到生产阶段的配方缩放的背景下。在这里，我们展示了将半自动化微流体系统与高通量表征仪器相结合，可以快速生产和表征LNP。与传统方法相比，高通量平板阅读器DLS提供了相当的流体动力学直径数据和更快的分析速度，尽管RNA定量灵敏度较低。此外，我们对动态光散射测量的原始自相关函数数据进行了独立分析，以减轻高通量仪器和单样品仪器之间的功能差异。基于荧光的分析，也能够进行高通量工作流程，被证明对RNA定量更敏感。这些结果表明，高通量系统可以简化LNP的开发，并集成到转化工作流程中，即筛选以确定命中配方，将命中配方转换为可扩展的生产方法，以及验证筛选表征结果。这种集成的工作流程代表了RNA治疗开发管道的重要一步，其中增加表征能力可以加速纳米药物的开发。

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引用次数: 0

Light-responsive α-TOS liposomal nanocarriers Co-delivering TiO2 and doxorubicin for the treatment of breast cancer 光响应α-TOS脂质体纳米载体共递送TiO2和阿霉素治疗乳腺癌。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-10 Epub Date: 2025-12-31 DOI: 10.1016/j.ijpharm.2025.126552

Kaixin Feng , Zhongkun Zhang , Jingjing Zhang , Xiaohan Xia , Siyu Yao , Yufei Wang , Min Wu

Doxorubicin (DOX) is limited by its clinical toxicity as a breast cancer therapy. Traditional liposomal formulations improve the tumor delivery of DOX but suffer from inadequate controlled release and low encapsulation efficiency of DOX. To address these, we developed a photo-responsive liposomal formulation DTTPL by co-encapsulating DOX and TiO₂ nanostructures (TiO₂) within D-α-tocopheryl succinate (α-TOS)-PEG liposomes. DTTPL successfully facilitated the release of DOX through the light-sensitive catalysis mechanism of TiO₂, exhibiting 4.6 times greater cytotoxicity against MCF-7 cells compared to free DOX. Transcriptional analysis revealed synergistic DOX/DTTPL dysregulation of key genes (Brca1, Bcl-2, Bax, Caspase-3), aligning with cytotoxicity. Eventually, light-triggered DOX/DTTPL formulation resulted in 70.09% of tumor growth inhibition (TGI) in mice with no significant organ toxicity. This photo-responsive nanoformulation enables efficient controlled release of DOX, offering an alternative strategy for small molecule delivery to treat triple negative breast cancer.

多柔比星（DOX）作为乳腺癌治疗的临床毒性受到限制。传统的脂质体制剂改善了DOX的肿瘤递送，但存在DOX控释不足和包封效率低的问题。为了解决这些问题，我们通过将DOX和TiO2纳米结构（TiO2）共包埋在D-α-生育酚琥珀酸酯(α-TOS)-PEG脂质体中，开发了光响应型脂质体DTTPL。DTTPL通过TiO2的光敏催化机制成功促进了DOX的释放，对MCF-7细胞的细胞毒性比游离DOX高4.6倍。转录分析显示DOX/DTTPL关键基因（Brca1、Bcl-2、Bax、Caspase-3）协同失调，与细胞毒性一致。最终，光触发DOX/DTTPL制剂在小鼠中产生70.09%的肿瘤生长抑制（TGI），没有明显的器官毒性。这种光响应纳米制剂能够有效地控制DOX的释放，为小分子递送治疗三阴性乳腺癌提供了一种替代策略。

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引用次数: 0

Assessing effects of leachables in single-use systems used in cell therapy manufacture 评估细胞治疗制造中使用的一次性系统中浸出剂的效果。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-10 Epub Date: 2025-12-21 DOI: 10.1016/j.ijpharm.2025.126522

Noemí Dorival-García , Gareth Lomasney , Jonathan Bones

Cell therapies (CT) have demonstrated life-changing benefits and curative options to patients with unmet medical needs. Recent commercial successes have strengthened support for the industry; strong clinical responses are propelling additional CT products toward commercialisation. However, manufacturing of CT products continues to create challenges. Extractables and leachables (E&Ls) are a significant concern for the CT industry, which relies exclusively on single-use systems (SUSs). Investigation of the impact of SUS materials that encounter the cell-based product is a new field and the generation of more information is critical. Here, a proof-of-principle study is presented, demonstrating evidence of effects of leachates on T cells. Jurkat cells, a prototypical T cell line, were cultivated in media previously incubated in single-used bags (SUBs) utilised during incubation/expansion stages. Leachables present in the media were identified by high resolution mass spectrometry (HRAM). The physiological condition of T-cells was assessed using biological assays. Media components and metabolites were analysed over time using a direct infusion-mass spectrometry (DI-MS) method. Media containing leachables resulted in cell growth inhibition and early onset of the apoptosis/necrosis pathways. Changes in mitochondrial membrane potential suggested that leachables are cytotoxic via ΔΨm depolarisation, involving the intrinsic apoptotic pathway in the initiation of cell death. Key metabolic pathways were also significantly affected, producing accumulation of toxic metabolites and degradation of nucleic acids and lipids.

细胞疗法（CT）已经证明了改变生活的好处和治疗选择的病人没有得到满足的医疗需求。最近的商业成功加强了对该行业的支持；强烈的临床反应正在推动更多的CT产品走向商业化。然而，CT产品的制造仍然面临挑战。可萃取物和可浸出物（E&L）是CT行业的一个重要问题，该行业完全依赖于一次性系统（SUSs）。研究SUS材料遇到细胞基产品的影响是一个新的领域，产生更多的信息是至关重要的。在这里，一个证明原则的研究提出，证明了渗滤液对T细胞的影响的证据。Jurkat细胞是一种典型的T细胞系，在培养基中培养，培养基以前在孵育/扩增阶段使用一次性袋（sub）孵育。采用高分辨率质谱法（HRAM）对介质中存在的可浸出物进行鉴定。采用生物学方法评估t细胞的生理状况。使用直接输注质谱法（DI-MS）分析培养基成分和代谢物随时间的变化。含有浸出剂的培养基导致细胞生长抑制和凋亡/坏死途径的早期发作。膜线粒体电位的变化表明，可浸出物通过ΔΨm去极化具有细胞毒性，涉及细胞死亡起始的内在凋亡途径。关键的代谢途径也受到显著影响，产生有毒代谢物的积累和核酸和脂质的降解。

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引用次数: 0

Poly (lactic-co-glycolic acid)-based microneedles for drug delivery across different biological barriers 基于聚（乳酸-羟基乙酸）的微针用于跨不同生物屏障的药物递送。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-10 Epub Date: 2025-12-28 DOI: 10.1016/j.ijpharm.2025.126529

Shelly Keisar , Qonita Kurnia Anjani , Abraham M. Abraham , Lalitkumar K. Vora , Eneko Larrañeta , Ryan F. Donnelly , Aiman Abu Ammar

Microneedles (MNs) are micro-sized needles that were originally designed as minimally invasive and painless devices capable of piercing the main skin barrier, the stratum corneum, without stimulating nerve fibers, showing promising prospects as an alternative to other drug administration routes. Poly (lactic-co-glycolic acid) (PLGA) is a biodegradable and biocompatible copolymer with favorable mechanical properties, making it particularly suitable for fabrication of MNs for controlled-release drug delivery. This review provides a comprehensive overview of the design, fabrication, and therapeutic potential of PLGA-based MN systems across a broad range of applications, including transdermal systemic delivery, vaccine delivery and topical skin applications. Due to their exceptional virtues, PLGA MNs are further utilized in nontransdermal applications such as ocular, oral cavity, nasal, and other emerging uses that are presented. Eventually, toxicity and safety profile are discussed, and a concluding section on future perspectives is provided.

微针（MNs）是一种微型针头，最初被设计为微创和无痛的装置，能够刺穿皮肤的主要屏障角质层，而不刺激神经纤维，作为其他给药途径的替代方案，具有很好的前景。聚乳酸-羟基乙酸（PLGA）是一种生物可降解和生物相容性共聚物，具有良好的机械性能，特别适用于制造用于控释药物递送的纳米颗粒。这篇综述全面概述了基于plga的MN系统的设计、制造和治疗潜力，包括经皮全身递送、疫苗递送和局部皮肤应用。由于其特殊的优点，PLGA MNs进一步应用于非透皮应用，如眼、口腔、鼻和其他新兴用途。最后，讨论了毒性和安全性，并提供了对未来前景的总结部分。

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引用次数: 0

Formulation development of a dapivirine-releasing subdermal implant for HIV prevention 预防HIV的释放达匹韦林皮下植入物的配方开发。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-10 Epub Date: 2025-12-26 DOI: 10.1016/j.ijpharm.2025.126524

Siqi Wang, Rand Z. Murtadha, R. Karl Malcolm

There have been several significant advances in recent years around long-acting strategies for HIV pre-exposure prophylaxis, including DapiRing® (a 1-month dapivirine (DPV)-releasing vaginal ring), Apretude® (a cabotegravir intramuscular injection administered every two months), and Yeztugo® (a twice-yearly lenacapavir injection). With the goal of developing new drug delivery devices that can extend antiretroviral release for 12 months or longer, we report here our preliminary efforts to design a subdermal implant releasing the antiretroviral drug DPV. These reservoir-type rod implants (length 40 mm, cross-sectional diameters 2.5, 3.2, 3.5 or 4.0 mm) comprised a silicone elastomer core containing solid crystalline DPV (loading 10, 20 or 40 % w/w) and an open-ended non-medicated rate-controlling silicone elastomer membrane (thickness 0.5, 0.8 or 1.0 mm). DPV in vitro release rates could be modulated by adjusting the membrane thickness. Continuous in vitro DPV release ∼12 μg/day was demonstrated over 330 days, with sufficient residual drug content (∼87 mg/∼95 %) to extend release for at least 5 years. In particular, the study highlights the challenges in designing subdermal implants providing sufficient DPV release to maintain systemic/vaginal concentrations at protective levels.

近年来，在HIV暴露前预防的长效策略方面取得了一些重大进展，包括DapiRing®（1个月的达匹韦林（DPV）释放阴道环）、Apretude®（每两个月一次的卡博特韦肌肉注射）和Yeztugo®（每年两次的lenacapavir注射）。为了开发新的药物输送装置，使抗逆转录病毒释放延长12 个月或更长时间，我们在这里报告了我们设计一种释放抗逆转录病毒药物DPV的皮下植入物的初步努力。这些储层式抽油杆植入物（长度40 mm，横截面直径2.5、3.2、3.5或4.0 mm）由含有固体结晶DPV（载荷为10、20或40 % w/w）的硅弹性体芯和开放式非药物控制速率的硅弹性体膜（厚度0.5、0.8或1.0 mm）组成。DPV的体外释放速率可以通过调节膜厚度来调节。在330 天内，DPV连续体外释放~ 12 μg/天，具有足够的残留药物含量（~ 87 mg/ ~ 95 %），延长释放至少5 年。该研究特别强调了设计皮下植入物以提供足够的DPV释放以维持全身/阴道浓度在保护水平的挑战。

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引用次数: 0

Cysteamine-eluting contact lenses: integrating in vitro, in vivo, and in silico approaches for ocular drug delivery 半胱氨酸洗脱隐形眼镜：整合体外、体内和计算机方法用于眼部药物输送。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-10 Epub Date: 2025-12-22 DOI: 10.1016/j.ijpharm.2025.126528

Anuj Chauhan , Sarbani Hazra , Brock Matter , Pankaj Kumar Sharma , Shilpa George , Aishee Dey , Bommanahalli Nagaraju Kumara , Uday B. Kompella

The objective of this study was to develop vitamin E nanobarrier contact lenses that can sustain the delivery of an equivalent amount of cysteamine to the cornea as eight drops per day regimen used in treating cystinosis. Senofilcon A lenses (14.0 mm diameter, −0.50 D power, 8.4 mm base curve) integrated with vitamin E and cysteamine were tested for drug release and fitted to the sink-release model to determine diffusivity and partition coefficient. The pharmacokinetics of cysteamine delivery by contact lenses and by control eye drops was measured in New Zealand white rabbits. Cysteamine delivery was modeled by a mechanistic model using contact lens parameters obtained from the in vitro studies along with known anatomical, physiological and drug specific parameters obtained from literature. The release duration of cysteamine increased from a few minutes in control lenses to about 2 and 6 h, in lenses loaded with 20 and 30 % vitamin E, respectively. In vivo studies showed that the contact lens-based approach can deliver significantly high concentrations compared to eye drops. The total mass of drug delivered by 20 % vitamin E loaded contact lens is more than six times the mass delivered by a single eye drop. The contact lens-based therapy achieves higher delivery than drops in the back of the eye tissues as well. The predictions of the mechanistic mathematical model are in good agreement with in vivo measurements for both eye drops and contact lenses. The contact lens-based delivery of cysteamine is a promising approach for replacing the multiple drop therapy.

这项研究的目的是开发维生素E纳米屏障隐形眼镜，这种隐形眼镜可以维持每天8滴等量的半胱胺到角膜，用于治疗胱氨酸病。将Senofilcon A透镜（直径14.0 mm， D功率-0.50，基曲线8.4 mm）与维生素E和半胱胺结合，进行药物释放测试，并拟合到沉淀释放模型以确定扩散系数和分配系数。研究了隐形眼镜和对照滴眼液给药半胱胺在新西兰大白兔体内的药代动力学。半胱胺的给药通过一个机制模型建模，该模型使用了从体外研究中获得的隐形眼镜参数以及从文献中获得的已知解剖、生理和药物特异性参数。在含有20%和30% %维生素E的晶状体中，半胱胺的释放时间分别从对照晶状体的几分钟增加到约2和6 h。体内研究表明，与滴眼液相比，基于隐形眼镜的方法可以提供明显更高的浓度。含有20% %维生素E的隐形眼镜所提供的药物总质量是一滴眼药水所提供的药物总质量的六倍多。这种基于隐形眼镜的疗法比在眼组织后面滴药的效果更好。机械数学模型的预测与眼药水和隐形眼镜的体内测量结果很好地一致。基于隐形眼镜的半胱胺递送是替代多次滴注治疗的一种有前途的方法。

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引用次数: 0

Alkaline phosphatase-triggered charge converting lipid nanoparticles: An innovative approach for oral nucleic acid delivery 碱性磷酸酶触发的电荷转化脂质纳米颗粒：一种口服核酸递送的创新方法。

IF 5.2 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics

Pub Date : 2026-02-10 Epub Date: 2026-01-02 DOI: 10.1016/j.ijpharm.2026.126554

Ilaria Polidori , Leonie Iris Weber , Stefan Keim , Dennis To , Markus Hartl , Andreas Bernkop-Schnürch

Enzyme-responsive lipid nanoparticles (LNPs) offer a promising strategy for oral nucleic acid delivery to gastrointestinal tumors. We hypothesized that coating LNPs with polyphosphates (PP) would enhance mucus penetration and enable charge conversion upon activation by intestinal alkaline phosphatase (IAP). The presence of the cell-penetrating peptide (CPP) stearyl-D-Arg₈ provides enhanced cellular uptake. LNPs were characterized regarding size, polydispersity index, zeta potential, charge conversion and evaluated for pH stability, behaviour in biorelevant fluids, and mucus diffusion. Plasmid DNA encoding for GFP or brain acid soluble protein-1 (BASP1) was encapsulated, and uptake and transfection were studied in intestinal cancer cell lines. Upon incubation with IAP, PP-coated D-Arg₈-LNPs released phosphate groups and underwent charge conversion. These particles remained stable across pH 1.5–9.0 and were more resistant to biorelevant fluids, though destabilization occurred with digestive enzymes. Compared to DOTAP- and D-Arg₈-LNPs, PP-coated LNPs showed superior mucus diffusion, cellular uptake, and transfection efficiency in hard-to-transfect Caco-2 and SW480 cells. Importantly, BASP1 expression from LNPs effectively suppressed SW480 proliferation. Overall, PP coated LNPs for oral administration can efficiently deliver nucleic acids into intestinal tumor cells, which may be suitable to interfere with the tumorigenic phenotype.

酶反应性脂质纳米颗粒（LNPs）为胃肠道肿瘤的口服核酸递送提供了一种很有前途的策略。我们假设用聚磷酸盐（PP）包裹LNPs可以增强黏液的渗透，并在肠道碱性磷酸酶（IAP）激活时实现电荷转换。细胞穿透肽（CPP） stearyl-D-Arg8的存在增强了细胞摄取。LNPs的特征包括大小、多分散性指数、zeta电位、电荷转换，以及pH稳定性、在生物相关流体中的行为和粘液扩散。包封编码GFP或脑酸溶蛋白-1 （BASP1）的质粒DNA，研究其在肠癌细胞系中的摄取和转染。经IAP孵育后，pp包被的D-Arg8-LNPs释放磷酸基团并进行电荷转换。这些颗粒在pH 1.5-9.0范围内保持稳定，并且对生物相关液体更具抵抗力，尽管消化酶会发生不稳定。与DOTAP-和D-Arg8-LNPs相比，pp包被的LNPs在难以转染的Caco-2和SW480细胞中表现出更好的粘液扩散、细胞摄取和转染效率。重要的是，来自LNPs的BASP1表达有效地抑制了SW480的增殖。综上所述，口服PP包被LNPs可以有效地将核酸传递到肠道肿瘤细胞中，可能适合干扰致瘤表型。

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引用次数: 0